X-Linked Huwe1 Is Essential for Oocyte Maturation and Preimplantation Embryo Development
Alaa A. Eisa,
Scott Bang,
Katherine J. Crawford,
Emily M. Murphy,
William W. Feng,
Souvik Dey,
Wendy Wells,
Ning Kon,
Wei Gu,
Lisa M. Mehlmann,
Srinivasan Vijayaraghavan,
Manabu Kurokawa
Affiliations
Alaa A. Eisa
Department of Medical Laboratories Technology, College of Applied Medical Sciences, Taibah University, Medina, Saudi Arabia
Scott Bang
Department of Biological Sciences, Kent State University, Cunningham Annex, Room A322, Kent, OH 44242, USA
Katherine J. Crawford
Department of Biological Sciences, Kent State University, Cunningham Annex, Room A322, Kent, OH 44242, USA
Emily M. Murphy
Department of Biological Sciences, Kent State University, Cunningham Annex, Room A322, Kent, OH 44242, USA
William W. Feng
Department of Biological Sciences, Kent State University, Cunningham Annex, Room A322, Kent, OH 44242, USA; Department of Molecular and Systems Biology, Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA
Souvik Dey
Department of Biological Sciences, Kent State University, Cunningham Annex, Room A322, Kent, OH 44242, USA
Wendy Wells
Department of Pathology, Dartmouth-Hitchcock Medical Center, Lebanon, NH 03756, USA
Ning Kon
Department of Pathology and Cell Biology, Columbia University, NY 10032, USA
Wei Gu
Department of Pathology and Cell Biology, Columbia University, NY 10032, USA
Lisa M. Mehlmann
Department of Cell Biology, UConn Health, Farmington, CT 06030, USA
Srinivasan Vijayaraghavan
Department of Biological Sciences, Kent State University, Cunningham Annex, Room A322, Kent, OH 44242, USA
Manabu Kurokawa
Department of Biological Sciences, Kent State University, Cunningham Annex, Room A322, Kent, OH 44242, USA; Department of Molecular and Systems Biology, Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA; Corresponding author
Summary: HUWE1 is a HECT-domain ubiquitin E3 ligase expressed in various tissues. Although HUWE1 is known to promote degradation of the tumor suppressor p53, given a growing list of its substrates, in vivo functions of HUWE1 remain elusive. Here, we investigated the role of HUWE1 in the female reproductive system. Homozygous deletion of Huwe1 in mouse oocytes of primary follicles caused oocyte death and female infertility, whereas acute depletion of HUWE1 protein by Trim-Away technology did not impact oocytes from antral follicles. Interestingly, oocytes from Huwe1 heterozygous females matured and fertilized normally, but the majority of embryos that lacked maternal Huwe1 were arrested at the morula stage after fertilization. Consequently, Huwe1 heterozygous females only produced wild-type pups. Concomitant knockout of p53 did not recover fertility of the Huwe1 knockout females. These findings make HUWE1 a unique and critical maternal factor indispensable for maintaining the quality of oocytes and embryos.
